For the past few years we have been involved in delineating the role of various uterine proteins in reproduction. In the rabbit uterus, two proteins, uteroglobin (UG) and transglutaminase (TG) are of interest to us. Uteroglobin is a small molecular weight, progesterone induced, pregnancy specific protein, suggested to play a role in immunological protection of the implanting embryo and the male gamets in the female genital tract. This was proposed to be accomplished by a crosslink formation between the cell surface proteins and UG, catalysed by TG. To produce a crosslink between cell surface proteins and UG both of these components have to be substrates of transglutaminase. Recently, Laki et al demonstrated that Beta2-microglobulin, a cell surface protein, is a substrate of transglutaminase. We have now shown that UG is also a substrate of TG since Tg can catalyse the polymerization of UG. This demonstration further supports the hypothesis that uterine proteins may crosslink with cell surface proteins and modify their immunological properties. Additionally, UG has been found to inhibit human and rabbit phagocyte chemotaxis in response to formyl peptide attractants in a dose dependent manner. Half-maximal inhibition was at 1.2 MuM. UG did not compete with formyl peptide for its receptor but inhibited internalization of radiolabeled formyl peptide. It is suggested that UG may not only crosslink with cell surface proteins but also may impair phagocyte migration to the uterus during pregnancy. More recently, UG was found to affect the aggregation of platelets induced by thrombin. This is an important observation since circulation through the microvasculature of the placenta requires that the blood be fluid at all times. UG may provide local anticoagulation to secure this process. Further work in progress is trying to delineate the mechanism by which UG prevents aggregation of the platelets.